Adell Teresa, Salò Emili, Boutros Michael, Bartscherer Kerstin
Department of Genetics and Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
Development. 2009 Mar;136(6):905-10. doi: 10.1242/dev.033761. Epub 2009 Feb 11.
Planarians can regenerate a whole animal from only a small piece of their body, and have become an important model for stem cell biology. To identify regenerative processes dependent on Wnt growth factors in the planarian Schmidtea mediterranea (Smed), we analyzed RNAi phenotypes of Evi, a transmembrane protein specifically required for the secretion of Wnt ligands. We show that, during regeneration, Smed-evi loss-of-function prevents posterior identity, leading to two-headed planarians that resemble Smed-beta-catenin1 RNAi animals. In addition, we observe regeneration defects of the nervous system that are not found after Smed-beta-catenin1 RNAi. By systematic knockdown of all putative Smed Wnts in regenerating planarians, we identify Smed-WntP-1 and Smed-Wnt11-2 as the putative posterior organizers, and demonstrate that Smed-Wnt5 is a regulator of neuronal organization and growth. Thus, our study provides evidence that planarian Wnts are major regulators of regeneration, and that they signal through beta-catenin-dependent and -independent pathways.
涡虫仅从身体的一小部分就能再生出完整的个体，因此成为干细胞生物学的重要模型。为了确定地中海涡虫（Schmidtea mediterranea, Smed）中依赖Wnt生长因子的再生过程，我们分析了Evi（一种Wnt配体分泌所特需的跨膜蛋白）的RNA干扰表型。我们发现，在再生过程中，Smed-evi功能缺失会阻止后端特征的形成，导致出现双头涡虫，类似于Smed-β-连环蛋白1 RNA干扰后的动物。此外，我们还观察到神经系统的再生缺陷，而在Smed-β-连环蛋白1 RNA干扰后并未出现这种情况。通过对再生涡虫中所有假定的Smed Wnt进行系统性敲低，我们确定Smed-WntP-1和Smed-Wnt11-2为假定的后端组织者，并证明Smed-Wnt5是神经元组织和生长的调节因子。因此，我们的研究表明，涡虫Wnt是再生的主要调节因子，并且它们通过β-连环蛋白依赖和非依赖途径发出信号。
